Anotherfamilyoflipid-sensingtranscriptionfactorsistheliver X receptor (LXR) family,whichiscomposedofLXRα andLXRβ.LXRα isexpressedprimarilyinadiposetissue,liver,intestine,andkidney,whereasLXRβ isubiquitouslyexpressed.LXRsarerelatedtoPPARsinthattheyaremembersofthenuclearhormonereceptorfamilyandheterodimerizewithRXR.LXRsarecholesterolsensors.Inhigh-cholesterolconditions,LXRsupregulateexpressionofATP-bindingcassette(ABC)proteins.Inthefaceofexcesscholesterol,LXRsalsoincreaseABCproteinexpressioninthegastrointestinaltract,whichpromoteseffluxofcholesterolfromenterocytestothelumenforexcretion.Mutationsinthesetransporters(ABCG5andABCG8)causesitosterolemia, characterizedbyexcessiveabsorptionofcholesterolandplantsterols.Intheliver,LXRspromoteconversionofcholesteroltobileacidsforexcretionortocholesterolestersforstorage.Inthelatteraction,LXRsincreaseSREBP1Cexpression,therebyincreasingthefattyacylCoAsneededforesterification.
of body weight that is accounted for by adipose tissue. About 25% of the variance in total body fat appears to be due to genetic factors. A genetic influence on fat mass is supported by (1) the tendency for the body mass of adopted children to correlate better with that of their biological parents than with that of their adoptive parents; (2) the greater similarity of adipose stores in identical (monozygotic) twins, whether reared together or apart, than in fraternal (dizygotic) twins; (3) the greater correlation between gains in body weight and abdominal fat in identical twins than in fraternal twins when they are fed a caloric excess; and (4) the discovery of several genes that cause obesity.
In addition, the gestational environment has a profound effect on body mass of the adult. The effect of maternal diet on the weight and body composition of offspring is called fetal programming. Low birth weights correlate with increased risk for obesity, cardiovascular disease, and diabetes. These findings suggest that the efficiency of fetal metabolism has plasticity and can be altered by the in utero environment. The development of a “thrifty” metabolism would be advantageous to an individual born to a mother